Statins Up Risk for Diabetes in High-Risk Patients

Long-term statin use may raise the risk of developing type 2 diabetes mellitus (T2DM) among individuals at high risk for the disease.
Several clinical trials of cardiovascular disease prevention with statins have reported increased risk of T2DM with statin therapy. However, these studies included participants at relatively low risk for diabetes.

A new study led by Jill Crandall, MD, of Albert Einstein College of Medicine, Bronx, New York, examined data on 3234 participants in the US Diabetes Prevention Program Outcomes Study. This randomized clinical trial looked at whether modest weight loss through lifestyle changes or treatment with metformin could reduce or delay development of T2DM among those at high risk. The participants received standard advice on healthy eating and exercise, and were randomly assigned to either an intensive lifestyle program, treatment with metformin, or placebo.

After a follow-up of 3 years, they were invited to take part in an outcomes study. Blood lipids and blood pressure were measured annually, and blood glucose levels measured twice a year.

The researchers published theirresults onlineOctober 23 in BMJ Open Diabetes Research & Care.

Risk seen in all taking statins

At the start of the study fewer than 4% of participants were taking statins, but use of these drugs gradually grew. After 10 years about one-third of the participants in all 3 groups were taking statins. The most commonly prescribed statins were simvastatin (40%) and atorvastatin (37%). The likelihood of a prescription rose substantially after a diagnosis of diabetes.

Statin use was associated with a 36% increased risk of developing diabetes for all three groups, accounting for age, sex, and ethnicity. After additional adjustment for blood pressure, cholesterol levels, baseline cardiovascular risk factors, and socioeconomic status, the increased risk was 27%.

The researchers grouped the drugs into low potency (pravastatin, lovastatin, fluvastatin) or high potency (atorvastatin, simvastatin, rouvastatin, cerivastatin), but found no link between statin potency and diabetes risk, and no difference in reduction in LDL-cholesterol. Longer statin use was significantly associated with greater diabetes risk.

Mechanisms unclear

The mechanisms underlying the effect of statins on development of diabetes are poorly understood, the researchers stated. Several studies have examined changes in insulin sensitivity during statin use, but the researchers saw no evidence of an effect of statins to modify insulin resistance, assessed as fasting insulin concentrations. Statins have been reported to reduce pancreatic beta-cell insulin secretion in vitro, but “the relevance to insulin secretion in vivo is not known,” they stated.

The study has several limitations. This was an observational study, with no firm conclusions about cause and effect. Also, statin prescriptions were based on an independent doctor's assessment, so patients were not randomly assigned to treatment, and information on dose was not available.

The benefits of statins need to be balanced against the risks, the researchers stated. “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”

They added that “nonetheless, glucose status should be monitored and healthy lifestyle behaviors reinforced in high-risk patients who are prescribed statins for cardiovascular disease prophylaxis.”